Drug models of schizophrenia
This selective review evaluates dopaminergic, glutamatergic, serotonergic, cannabinoid, GABAergic, cholinergic and kappa‑opioid drug models for their similarity to schizophrenia and argues that integrating interactions among these neurotransmitter systems, rather than relying on any single model, is essential to form coherent pathogenesis hypotheses and identify new therapeutic targets.
Authors
- Robin Carhart-Harris
- James Stone
Published
Abstract
Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia.
Research Summary of 'Drug models of schizophrenia'
Introduction
Steeds and colleagues frame the review by emphasising that existing antipsychotic medications act primarily by blocking dopamine D2 receptors, but that a substantial proportion of patients do not achieve full remission or continue to experience negative symptoms and cognitive impairment. The introduction highlights the clinical need for novel therapeutic targets and for models that can help identify and screen new compounds, noting that antipsychotics differ little in efficacy (except clozapine) and that side effects and long-term adherence are major problems. The review sets out to evaluate pharmacological drug models that have been used to mimic aspects of schizophrenia in humans and animals. Specifically, the authors compare dopaminergic, glutamatergic, serotonergic, endocannabinoid, GABAergic, cholinergic and kappa-opioid models, consider neurochemical evidence linking these systems to schizophrenia, and assess how well each model reproduces positive, negative and cognitive symptom domains. They also note up front that purely pharmacological models are necessarily incomplete for a chronic, neurodevelopmental and episodic illness such as schizophrenia, but can nevertheless illuminate mechanisms for particular symptom domains and help prioritise novel drug targets.
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Study Details
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- APA Citation
Steeds, H., Carhart-Harris, R. L., & Stone, J. M. (2015). Drug models of schizophrenia. Therapeutic Advances in Psychopharmacology, 5(1), 43-58. https://doi.org/10.1177/2045125314557797
References (10)
Papers cited by this study that are also in Blossom
Carhart-Harris, R. L., Brugger, S., Nutt, D. J. et al. · Journal of Psychopharmacology (2013)
Carhart-Harris, R. L., Erritzoe, D., Williams, T. et al. · PNAS (2012)
Carhart-Harris, R. L., Leech, R., Erritzoe, D. et al. · Schizophrenia Bulletin (2012)
Carter, O., Burr, D. C., Pettigrew, J. D. et al. · Journal of Cognitive Neuroscience (2006)
William Deakin, J. F., Lees, J., McKie, S. et al. · JAMA Psychiatry (2008)
Geyer, M. A., Vollenweider, F. X. · Trends in Pharmacological Sciences (2008)
Johnson, M. W., Maclean, K. A., Reissig, C. J. et al. · Drug and Alcohol Dependence (2011)
Maclean, K. A., Johnson, M. W., Reissig, C. J. et al. · Psychopharmacology (2012)
Quednow, B. B., Kometer, M., Geyer, M. A. et al. · Neuropsychopharmacology (2011)
Ranganathan, M., Schnakenberg, A., Skosnik, P. D. et al. · Biological Psychiatry (2012)
Cited By (6)
Papers in Blossom that reference this study
Dourron, H. M., Strauss, C., Hendricks, P. S. · Pharmacological Reviews (2022)
Barrett, F. S., Krimmel, S. R., Griffiths, R. R. et al. · NeuroImage (2020)
Schmidt, A., Müller, F., Lenz, C. et al. · Psychological Medicine (2017)
Lewis, C. R., Preller, K. H., Kraehenmann, R. et al. · NeuroImage (2017)
Dos Santos, R. G., Balthazar, F. M., Bouso, J. C. et al. · Journal of Psychopharmacology (2016)
Das, S., Barnwal, P., Ramasamy, A. et al. · Therapeutic Advances in Psychopharmacology (2016)
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